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Pleomorphic RhabdomyosarcomaPhase 2NCT02050919

Sorafenib Tosylate, Combination Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With High-Risk Stage IIB-IV Soft Tissue Sarcoma

A Phase 2 study testing Epirubicin Hydrochloride, External Beam Radiation Therapy and Ifosfamide in people with Pleomorphic Rhabdomyosarcoma and Stage IIB Adult Soft Tissue Sarcoma AJCC v7, run by OHSU Knight Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase II trial studies how well sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery work in treating patients with high-risk stage IIB-IV soft tissue sarcoma. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Epirubicin Hydrochloride, External Beam Radiation Therapy and Ifosfamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
3 Dec 2013to 31 Dec 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed, soft-tissue sarcoma: excluding rhabdomyosarcoma (pleomorphic rhabdomyosarcoma patients are eligible), Ewing's, primitive neuroectodermal tumor (PNET), osteosarcoma, or gastrointestinal stromal tumor
  • American Joint Committee on Cancer (AJCC) (7th edition) stage IIb, III, or IV patients planned for resection of the primary tumor
  • > 5 cm in greatest dimension
  • Intermediate or high-grade
  • Superficial or deep
  • Sarcoma located on upper (includes shoulder) or lower (includes hip) extremities or on body wall
Show all 24Show fewer
  • Intermediate or high-grade: grades 2 or 3 on scale of 1-3
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Hemoglobin (Hgb) >= 9.0 g/dL
  • Platelets >= 100,000/uL
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 1.5 x ULN
  • International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits; patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate; for patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable
  • No prior chemotherapy, radiation, or biotherapy
  • No major surgery within 4 weeks prior to study entry
  • No contraindications to limb-sparing surgery; patient should be evaluated by a surgeon who specializes in sarcoma resections prior to study enrollment to ensure patient (pt) is a candidate for limb-sparing surgery
  • No severe peripheral vascular disease
  • Adequate contraception must be used and patients must not be pregnant or breastfeeding; women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; men and women should use adequate birth control for at least thirty days after the last administration of sorafenib
  • Women of childbearing potential must have negative serum pregnancy test performed within 7-days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Patient must sign a study-specific consent form prior to registration
  • Ability to understand and the willingness to sign a written informed consent; a signed informed consent must be obtained prior to any study specific procedures

Who cannot join

  • Patients with known brain metastases; patients with neurological symptoms must undergo a computed tomography (CT) scan/magnetic resonance imaging (MRI) of the brain to exclude brain metastases
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection > Common Terminology Criteria for Adverse Events (CTCAE) grade 2, symptomatic congestive heart failure, unstable angina pectoris, cardiac ventricular arrhythmia requiring anti-arrhythmic therapy, or psychiatric illness/social situations that would limit compliance with study requirements; patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management
  • Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event >= CTCAE grade 2 within 4 weeks of first dose of study drug
Show all 18Show fewer
  • Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
  • Serious non-healing wound, ulcer, or bone fracture
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery or significant traumatic injury within 4 weeks of first study drug
  • Use of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem
  • Pregnant or lactating women are excluded from this study
  • Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not to be registered; patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse
  • Any uncontrolled thyroid disease
  • Requirement for hemodialysis or peritoneal dialysis

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase II Study of Sorafenib With Chemotherapy, Radiation, and Surgery for High-Risk Soft Tissue Sarcomas

This phase II trial studies how well sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery work in treating patients with high-risk stage IIB-IV soft tissue sarcoma. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin hydrochloride and ifosfamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x rays to kill tumor cells. Giving sorafenib tosylate, combination chemotherapy, radiation therapy, and surgery may be an effective treatment for soft tissue sarcoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the pathologic response rate (>= 95% necrosis) after preoperative treatment with sorafenib (sorafenib tosylate), epirubicin (epirubicin hydrochloride), ifosfamide, and hypofractionated radiation for high risk soft tissue sarcomas of the extremities or body wall.

SECONDARY OBJECTIVES:

  1. To further characterize the safety of sorafenib plus chemoradiotherapy, including wound complication rate.

II. To estimate time-to-event rates, including overall survival, overall disease-free survival, distant disease-free survival, and local disease-free survival in patients with high risk soft tissue sarcomas of the extremities or body wall treated with preoperative sorafenib plus chemoradiotherapy and postoperative sorafenib plus chemotherapy.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) once daily (QD) on days 1-71 and 85-155, epirubicin hydrochloride intravenously (IV) over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo external beam radiation therapy (EBRT) on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 1 year, and then yearly for 2 years.

Being tested
Epirubicin Hydrochloride, External Beam Radiation Therapy, Ifosfamide, Laboratory Biomarker Analysis, Sorafenib Tosylate
Medical subject headings
Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Epirubicin HydrochlorideDrug

    Also called Ellence, IMI-28, Pharmorubicin PFS

    Given IV

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiotherapy, External Beam RT

    Undergo EBRT

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Sorafenib TosylateDrug

    Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib

    Given PO

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgical resection

Study groups in NCT02050919
Study groupRoleWhat they receive
Treatment (sorafenib, chemotherapy, radiation, surgery)ExperimentalPatients receive sorafenib tosylate PO QD on days 1-71 and 85-155, epirubicin hydrochloride IV over 3-5 minutes, and ifosfamide IV over 90 minutes on days 15-17, 36-38 (ifosfamide only), 57-59, 99-101, 120-122, and 141-143. Patients undergo EBRT on days 36-45 and surgical resection on day 78. Patients with positive margins, undergo EBRT boost on days 91-98.
Receives: Drug: Epirubicin Hydrochloride; Radiation: External Beam Radiation Therapy; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Drug: Sorafenib Tosylate; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis.

    Descriptive statistical analysis will be conducted. The proportion with 95% confidence interval will be summarized.

    Measured: Assessed at surgical resection

Secondary outcomes (6)

  1. Number of Grade 3-4 Adverse Events

    Measured as the number of Grade 3-4 Adverse Events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0

    Measured: Up to 5 years

  2. Number of Participants With Wound Complications

    Wound complication rate, including 1) any secondary operation for wound repair, or 2) wound management without secondary operation including invasive procedures without general or regional anesthesia, readmission for wound care, or persistent deep packing for 120 days or longer.

    Measured: At least 120 days

  3. Overall Survival at 2 Years

    Percentage of patients alive at 2 years, Method of Kaplan-Meier used.

    Measured: Time from registration until death from any cause

  4. Overall Disease-free Survival (Stage IIB-III Patients)

    Time from surgical resection to local recurrence, distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier \used.

    Measured: Time from surgical resection to local recurrence, distant metastatic disease, or death, whichever occurs first, assessed up to 2 years

  5. Distant Disease-free Survival (Stage IIB-III Patients)

    Time from registration to development of distant metastatic disease or death, subjects with stage IV disease excluded. Method of Kaplan-Meier used.

    Measured: Time from registration until development of distant metastatic disease or death, whichever occurs first, assessed up to 2 years

  6. Number of Participants With Local Recurrence

    Number of patients with local recurrence after surgical resection of the primary tumor

    Measured: Time from surgical resection until primary analysis ( Median follow-up for local recurrence 17.11 months, range 6.18 - 42.8 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2014 (estimated)
  2. Study start3 Dec 2013
  3. Primary completion7 May 2018
  4. Study completion31 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02050919
Sponsor's protocol ID
IRB00009464
Other IDs
NCI-2013-02414, IRB00009464
Status last verified
Feb 2022
First submitted
29 Jan 2014
Last updated
21 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Vatner R, James CD, Sathiaseelan V, Bondra KM, Kalapurakal JA, Houghton PJ. Radiation therapy and molecular-targeted agents in preclinical testing for immunotherapy, brain tumors, and sarcomas: Opportunities and challenges. Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28439. doi: 10.1002/pbc.28439. Epub 2020 Aug 22.

    PubMed 32827353

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Epirubicin Hydrochloride, External Beam Radiation Therapy and Ifosfamide in people with Pleomorphic Rhabdomyosarcoma and Stage IIB Adult Soft Tissue Sarcoma AJCC v7, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Response Rate, Defined as the Percentage of Participants With Greater Than or Equal to 95% Necrosis. (time frame: Assessed at surgical resection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02050919, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2022.

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